Evidence map›Paper›PMID 39251091›Full record

ArticleJournal of hepatology2025

Assessment of liver graft quality during hypothermic oxygenated perfusion: The first international validation study.

Jahnina Eden, Adam M Thorne, Silke B Bodewes, Damiano Patrono, Dorotea Roggio, Eva Breuer, Caterina Lonati, Daniele Dondossola, Guergana Panayotova, Amanda P C S Boteon and 26 more

Abstract readValidation StudyMulticenter Study
In one paragraph

Article in Journal of hepatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Trial
  4. A diagnostic accuracy study of mitochondrial FMN during hypothermic oxygenated perfusion to guide liver utilization and avoid normothermic assessment.Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society · 2026
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  15. Time as a Therapeutic Ally: The Promise of Long-Term Solid Organ and Tissue Perfusion.Transplant international : official journal of the European Society for Organ Transplantation · 2026
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  18. [Research progresses in ex vivo liver perfusion technology].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

36 authors.

Jahnina EdenDepartment of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland; Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.
Adam M ThorneDepartment of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.
Silke B BodewesDepartment of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.
Damiano PatronoGeneral Surgery 2U-Liver Transplant Unit, Department of Surgery, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
Dorotea RoggioGeneral Surgery 2U-Liver Transplant Unit, Department of Surgery, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
Eva BreuerDepartment of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland.
Caterina LonatiGeneral and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Centre of Preclinical Research, Milan, Italy, Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza 35, 20100, Milan, Italy.
Daniele DondossolaGeneral and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Centre of Preclinical Research, Milan, Italy, Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza 35, 20100, Milan, Italy.
Guergana PanayotovaDepartment of Surgery, Division of Transplant and HPB Surgery, Rutgers NJMS/University Hospital, Newark, NJ, USA.
Amanda P C S BoteonLiver Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil.
Daniel WalshIndependent Researcher, Cardiff, UK.
Mauricio Flores CarvalhoDepartment of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Ivo J SchurinkDepartment of Surgery, Division of HPB and Transplant Surgery, Erasmus MC Transplant Insititute, University Medical Center, Rotterdam, the Netherlands.
Fariha AnsariFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY, 10065, USA.
Dagmar KollmannDivision of Transplantation, Department of Surgery, Medical University of Vienna, Wien, Austria.
Giuliana GerminarioHepatobiliary and Transplant Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
Elisabeth Alexis Rivas GarridoHepato-Pancreato-Biliary Surgery Unit, Surgery Service, Complejo Asistencial Dr. Sótero Del Río and Institute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
Julio BenitezHepato-Pancreato-Biliary Surgery Unit, Surgery Service, Complejo Asistencial Dr. Sótero Del Río and Institute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
Rolando RebolledoHepato-Pancreato-Biliary Surgery Unit, Surgery Service, Complejo Asistencial Dr. Sótero Del Río and Institute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
Matteo CesconHepatobiliary and Transplant Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
Matteo RavaioliHepatobiliary and Transplant Surgery Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Sant'Orsola-Malpighi Hospital, Bologna, Italy; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
Gabriela A BerlakovichDivision of Transplantation, Department of Surgery, Medical University of Vienna, Wien, Austria.
Jeroen De JongeDepartment of Surgery, Division of HPB and Transplant Surgery, Erasmus MC Transplant Insititute, University Medical Center, Rotterdam, the Netherlands.
Deniz UlukDepartment of Surgery, Campus Charité Mitte, Campus Virchow-Klinikum-Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.
Isabella LurjeDepartment of Surgery, Campus Charité Mitte, Campus Virchow-Klinikum-Charité-Universitätsmedizin Berlin, Berlin, Germany.
Georg LurjeDepartment of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany; Department of Surgery, Campus Charité Mitte, Campus Virchow-Klinikum-Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.
Yuri L BoteonLiver Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil.
James V GuarreraDepartment of Surgery, Division of Transplant and HPB Surgery, Rutgers NJMS/University Hospital, Newark, NJ, USA.
Renato RomagnoliGeneral Surgery 2U-Liver Transplant Unit, Department of Surgery, A.O.U. Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
Alexander GalkinFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, 407 East 61st Street, New York, NY, 10065, USA.
David MeierhoferMax Planck Institute for Molecular Genetics, Mass Spectrometry Facility, Berlin, Germany.
Robert J PorteDepartment of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.
Pierre Alain ClavienDepartment of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland.
Andrea SchlegelDepartment of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland; General and Liver Transplant Surgery Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Centre of Preclinical Research, Milan, Italy, Department of Pathophysiology and Transplantation, University of Milan, Via Francesco Sforza 35, 20100, Milan, Italy; Transplantation Center, Digestive Disease and Surgery Institute and Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Vincent E de MeijerDepartment of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.
Philipp DutkowskiDepartment of Surgery and Transplantation, Swiss HPB Centre, University Hospital Zurich, Switzerland; Division of Visceral Surgery, University Digestive Health Care Centre Clarunis, University Hospital Basel, Switzerland. Electronic address: philipp.dutkowski@usb.ch.

Funding

The Role of FMN Loss by Mitochondrial Complex I in Neonatal Hypoxic-Ischemic Brain InjuryR01NS112381 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI GALKIN, ALEXANDER · 2020 to 2024
$2.1M
Metabolic Landscape and Mitochondrial ROS Balance in Brain Ischemia/ReperfusionR01NS131322 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI Alexander Galkin, Steven S Gross · 2024 to 2026
$1.6M
Molecular Targets of Preservation Injury Mitigated by Hypothermic Oxygenated Machine Perfusion in Liver TransplantationR21AI180739 · NIAID · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · PI GUARRERA, JAMES V., LUNSFORD, KERI ELIZABETH · 2024 to 2025
$426k
NIAID NIH HHS R21 AI180739NINDS NIH HHS R01 NS112381NINDS NIH HHS R01 NS131322
6 · The paper itself

Abstract

BACKGROUND &

aimsWhile it is currently assumed that liver assessment is only possible during normothermic machine perfusion, there is uncertainty regarding a reliable and quick prediction of graft injury during ex situ hypothermic oxygenated perfusion (HOPE). We therefore intended to test, in an international liver transplant cohort, recently described mitochondrial injury biomarkers measured during HOPE before liver transplantation.

methodsPerfusate samples of human livers from ten centers in seven countries with HOPE experience were analyzed for released mitochondrial compounds, i.e. flavin mononucleotide (FMN), NADH, purine derivatives and inflammatory markers. Livers deemed unsuitable for transplantation served as negative controls.

resultsWe collected 473 perfusate samples of human donation after cardiac death (n = 315) and donation after brain death (n = 158) livers. Fluorometric assessment of FMN in perfusate was validated by mass spectrometry (R = 0.7011, p <0.0001). Graft loss due to primary non-function or cholangiopathy was predicted by perfusate FMN values (c-statistic mass spectrometry 0.8418, 95% CI 0.7466-0.9370, p <0.0001; c-statistic fluorometry 0.7733, 95% CI 0.7006-0.8461, p <0.0001). Perfusate FMN values were also significantly correlated with symptomatic non-anastomotic strictures and kidney failure, and superior for the prediction of graft loss than conventional scores derived from donor and recipient parameters, such as the donor risk index and the balance of risk score. Mitochondrial FMN values in liver tissues of non-utilized livers were low, and inversely correlated to high perfusate FMN values and purine metabolite release.

conclusionsThis first international study validates the predictive value of the mitochondrial cofactor FMN, released from complex I during HOPE, and may therefore contribute to a better risk stratification of injured livers before implantation. IMPACT AND IMPLICATIONS: Analysis of 473 perfusates, collected from ten international centers during HOPE (hypothermic oxygenated perfusion), revealed that mitochondria-derived flavin mononucleotide values in perfusate are predictive of graft loss, cholangiopathy, and kidney failure after liver transplantation. This result is of high clinical relevance, as recognition of graft quality is urgently needed to improve the safe utilization of marginal livers. Ex situ machine perfusion approaches, such as HOPE, are therefore likely to increase the number of useable liver grafts.

Indexed as

Hypothermia, InducedLiverLiver TransplantationOrgan PreservationPerfusionAdultAgedBiomarkersFemaleFlavin MononucleotideHumansMaleMiddle AgedOxygenBiomarkersFlavin MononucleotideOxygenhypothermic machine perfusionliver transplantationliver utilizationmitochondriaoutcomeviability assessment

Identifiers

PMID39251091
PMCPMC11830552

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